Over the past 3 1/2 years over 1,800 cases of the Acquired Immune Deficiency Syndrome (AIDS) have been reported to the Disease Control. Epidemiologic features of the syndrome suggest that one or more transmissable agents may be operative in the pathophysiology of AIDS. Human T-cell leukemia (HTLV), a T-lymphotropic virus initially described in association with an aggressive variant of mycosis fungoides, appears to be etiologic for a form of leukemia endemic to Southern Japan. The tropism of HTLV for T-cells of the surface phenotype most severely depleted in AIDS, and the finding of an increased frequency of antibodies in serum from patients with, or at high risk for, AIDS reactive with antigens on the surface of HTLV transformed cell has led to speculation that HTLV or an HTLV-like agent might be involved in the induction of AIDS. In addition, reports of DNA sequences hybridizing with HTLV probes in cultured lymphocytes from two patients with AIDS, and the isolation of an apparent HTLV variant from a French patient at high risk for AIDS have further fueled this speculation. The HTLV seronegativity of a large fraction of AIDS patients, and the extreme difficulties which have so far been encountered in demonstrating the virus in materials from AIDS patients have raised doubt about this agent being etiologic for AIDS. The human herpesviruses, CMV and EBV, are potent immunomodulators which have been associated with the tumors most frequently encountered in AIDS patients, Kaposi's sarcoma and B-cell lymphoma. These agents ate, however, ubiquitous and no evidence has emerged that there are unique strains of CMV or EBV in patients with AIDS. Prior studies with HTLV have focused primarily on the humoral immune response to the virus. Activity of interferons against other retroviruses has been previously demonstrated. We plan to study the interferon sensitivity of HTLV in vitro, to study several aspects of the cell mediated immune response to HTLV, and to examine potential interactions between HTLV and EBV or CMV in vitro. It is anticipated that these studies will provide further insight into the possible relationship between HTLV or HTLV-like agents and AIDS, and may shed light on potential treatment modalities for HTLV-related diseases.